Methamphetamine and cocaine are powerful stimulant drugs of abuse that act, in large part, by increasing dopaminergic transmission in the brain. The attraction to stimulant use may begin with individual desire to combat disorders of excessive sleepiness, and drug dependence may be reinforced, in part, by hypersomnolence on drug withdrawal. Increased NonREM sleep time, sleep episode duration, and EEG delta power reflect the normal compensatory sleep responses (CSR) to extended wakefulness. Catecholamine releasing stimulants (e.g., methamphetamine) potently induce CSR; however little is known about acute psychostimulant interaction with sleep homeostasis or the consequences of chronic stimulant use on CSR mechanisms. Preliminary studies indicate that wakefulness induced by dopamine reuptake blockers, including cocaine, produce no CSR, suggesting interactions with sleep homeostatic mechanisms that are distinct from amphetamines. Cholinergic neurons in the nucleus basalis (NBM), nucleus accumbens, and adjacent regions receive dopaminergic input from the ventral tegmental area that are implicated in the activating properties of psychostimulants and their abuse potential. Thus, cocaine effects on sleep are likely to be mediated directly in this region. Given the role of adenosine as an endogenous sleep factor in the basal forebrain, adenosine levels in this region may interact differently with cocaine and methamphetamine-induced dopaminergic influences on the NBM. The proposed research will investigate acute and chronic cocaine and methamphetamine interaction with sleep homeostasis in terms of its generality, involvement of the basal forebrain, interaction with sleep deprivation, and interaction with adenosinergic mechanisms that also modulate sleep-wakefulness. Four interrelated specific aims will examine acute and chronic stimulant interaction with sleep homeostasis using computerized sleep recording, microinjection, and in vivo microdialysis techniques in rats. We will test the hypotheses that: 1.) wakefulness induced by acute cocaine treatment is uncoupled from the sleep homeostatic process; 2.) cocaine and methamphetamine act locally on dopamine terminals in the nucleus basalis to produce wakefulness; 3.) methamphetamine increases basal forebrain adenosine levels or adenosine receptor responsiveness significantly more than cocaine; 4.) wakefulness induced by chronic cocaine administration remains uncoupled from the normal sleep homeostatic mechanisms that invoke CSR, and drug tolerance reduces CSR to sleep deprivation during psychostimulant administration. The proposed studies will advance our understanding of dopaminergic stimulant interactions with sleep homeostasis, CSR mechanisms, and their respective contributions to hypersomnolence associated with drug withdrawal and drug dependence.